DESCRIPTION Abstract: There are currently 14 million U.S Veterans over the age of 55 according to the 2010 U.S. Census. Research has indicated that motor declines begin to accelerate within this age group and beyond as does incidence of motor pathology. Aerobic exercise is currently under investigation for its potential in increasing cortical plasticity and offering improved outcome for rehabilitation of motor disorders. Exciting new studies (* denotes VA sponsored research) present the possibility that aerobic exercise may lead to significant improvements in upper extremity function (McGregor et al., 2009*; McGregor et al., 2011*; Voelcker-Rehage et al., 2010; Ploughman et al., 2008) in both aging and disease. However, the mechanisms by which fitness exerts its benefits have yet to be fully understood. New research has shown that upper extremity performance is associated with aging-related losses in interhemispheric inhibition (Bernard & Seidler, 2011; Fling & Seidler, in press; McGregor et al., 2009), which begins even in middle age. Our lab has recently shown that these changes may not be inevitable or immutable. New evidence indicates increased levels of physical fitness through aerobic activity may mitigate losses in interhemispheric inhibition and improve motor performance. This research proposes to enroll sedentary older Veterans into a program consisting of upper extremity behavioral training and regular engagement in physical activity. We hypothesize that motor performance will be linked to levels of interhemispheric inhibition (assessed by advanced neuroimaging) and both will improve over the course of our exercise intervention. We believe this research is critical to our understanding of normal motor organization and how it changes due to aging processes will inform our capability for reclamation of motor capacity due to neural pathology, as cortical activation patterns may vary according to biological age. The goal is that this work will eventually be applied to rehabilitation of motor deficits, which occur with increase incidence within and beyond middle age. PUBLIC HEALTH RELEVANCE: This study aims to enroll sedentary older Veterans into a program of upper extremity training and physical activity. The study will provide Dr. McGregor with a strong mentorship vehicle with which he will progress towards independence as an VA-ORD scientist. We hypothesize that motor performance will be linked to levels of inter-hemispheric inhibition, and both will improve from the intervention, as will Veterans' functional independence The area of research described in the proposed CDA-2 has strong implications relevant to the rehabilitative needs of Veterans as it is an intervention designed to improve quality of life in multiple facets of Veterans civilia life. Therefore, this study has the potential to lead to efficacious interventions that can translae into improved quality of life for Veterans. Further, it will aid the continued development of Dr. McGregor and his strong commitment to the Department of Veterans Affairs.